RESEARCH PROJECTS

Osteoarthritis
Pathogenesis and Therapy

Articular cartilage has a unique organization
of matrix macromolecules synthesized and maintained by chondrocytes.
Large aggregating proteoglycans are highly negatively charged
and produce an osmotic swelling pressure that resists compression.
This swelling pressure is counter-balanced by the restraining
force of a collagen fibrillar network composed primarily
of type II and type XI collagens interconnected with type
IX collagen. In addition to the major structural molecules,
cartilage also contains an abundance of other matrix components
including small proteoglycans, adhesion and connecting molecules,
and various growth factors. Together, these extracellular
matrix components provide the biomechanical properties of
articular cartilage necessary for smooth joint movement and
the distribution of load.

Osteoarthritis is characterized by a progressive degeneration
of articular cartilage and increasingly compromised joint
function. While initiating events are variable and can include
developmental and/or acquired components, disease progression
involves many common pathways. Cartilage matrix components
are broken down and the normal balance between their synthesis
and degradation is lost. Over time, the structural integrity
of articular cartilage fails and joint movement becomes increasingly
painful and restricted. Our research is focused on how chondrocyte
function changes during the development and progression of
osteoarthritis.

How do chondrocytes contribute to the pathogenesis of
this disease?

What limits their ability to maintain the structural
integrity of cartilage matrix?

How do therapeutic strategies used in patients suffering
from osteoarthritis impact chondrocyte function?

Osteoarthritic
cartilage illustrating a loss of structural integrity on
the joint surface.